Induction of acute cholecystitis by activation of factor XII.

Acute, acalculous cholecystitis is seen among patients suffering with bacterial sepsis, burns, trauma, or cancer; clinical conditions that could lead to activation of factor XII-dependent pathways and result in inflammation of the gall bladder. To test this hypothesis, dogs were injected intravenously with ellagic acid or rutin, known polyphenol activators of factor XII, or with Escherichia coli endotoxin, also known to activate factor XII, and monkeys were injected intravenously with ellagic acid. In both species, in vivo activation of factor XII-dependent pathways with polyphenol activator resulted in rapid and selective development of acute vasculitis in the serosa and muscularis of the gallbladder and margination of polymorphonuclear neutrophils in pulmonary blood vessels. Intravenous injection of E. coli endotoxin in dogs resulted in necrosis and thrombosis of vessels that were especially severe in the serosa and muscularis of the gallbladder but also present in vessels of many other organs. These observations indicate that blood vessels of the gall bladder and, to a lesser degree, the lung are especially sensitive to injury consequent to in vivo activation of factor XII-dependent pathways and, in view of the common ingestion of plant polyphenols, may provide important insight into the pathogenesis of cholecystitis in man.